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Rationale: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up., Patients and Methods: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m 2 and CDDP 100 mg/m 2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives., Results: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months., Conclusion: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Results from the phase 3 PRODIGE 23 study showed that neoadjuvant chemotherapy (NAC) with mFOLFIRINOX and preoperative chemoradiotherapy improved disease-free survival compared with preoperative chemoradiotherapy in patients with locally advanced rectal cancer. We aimed to assess the health-related quality of life (HRQOL) outcomes from this study., Patients and Methods: A total of 461 patients (231 versus 230 patients) from 35 French hospitals were randomly assigned to either NAC with FOLFIRINOX (oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 , fluorouracil 2400 mg/m 2 over 46 h intravenously every 2 weeks for 6 cycles) followed by preoperative chemoradiotherapy or chemoradiotherapy only. HRQOL was assessed at baseline, during treatments and at 2-year follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires., Results: Compared to baseline, HRQOL scores during NAC were better for tumour symptoms but worse for global health status, functional domains, fatigue, nausea/vomiting and appetite loss. During follow-up, improved emotional functioning was observed, but deterioration of body image, increased urinary incontinence, and lower male sexual function were observed. Linear mixed model exhibited a treatment-by-time interaction effect for nausea/vomiting and insomnia symptoms showing a greater deterioration in the standard-of-care group. Only treatment arm and baseline physical functioning were independent significant favourable prognostic factors., Conclusion: NAC improved tumour-related symptoms and transitorily reduced most functional scores. Adding NAC before chemoradiotherapy and increased physical functioning at baseline were independent significant prognostic factors for longer disease-free survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The role of chemotherapy has not been established in the treatment of metastatic squamous cell oesophageal cancer (mESCC)., Patients and Methods: E-DIS is a discontinuation trial, aimed at estimating efficacy, quality of life and safety of chemotherapy continuation (CT-CONT) in patients with mESCC who are free from progression after a selection phase of chemotherapy. The primary end-point was overall survival., Results: Sixty-seven patients were randomised. The 9-month survival rate was 50% (85% confidence interval [CI]: 37-62%) and 48% (85% CI: 35-60%) in the CT-CONT arm and in the chemotherapy discontinuation (CT-DISC) arm, respectively. The time until definitive deterioration of the global health status (European Organisation for Research and Treatment of Cancer [EORTC] core quality of life questionnaire) was 6.6 months (95% CI: 3.3-12.4) for the CT-CONT arm and 4.2 months (95% CI: 2.9-6.3) for the CT-DISC arm, with a hazard ratio (HR CT-DISC/CT-CONT ) = 1.44 (95% CI: 0.82-2.53). We observed a beneficial trend in favour of CT-CONT (HR > 1) for most dimensions, including an improvement for three dimensions (dysphagia, eating and oesophageal pain) of the EORTC Oesophageal Cancer Module QLQ-OES18., Conclusion: CT-CONT provides an overall survival rate that is similar to CT-DISC. E-DIS trial provides valuable data to support shared decision-making between physicians and patients regarding CT-CONT/DISC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: To optimise measurement precision, relevance to patients and flexibility, patient-reported outcome measures (PROMs) should ideally be adapted to the individual patient/study while retaining direct comparability of scores across patients/studies. This is achievable using item banks and computerised adaptive tests (CATs). The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) is one of the most widely used PROMs in cancer research and clinical practice. Here we provide an overview of the research program to develop CAT versions of the QLQ-C30's 14 functional and symptom domains., Methods: The EORTC Quality of Life Group's strategy for developing CAT item banks consists of: literature search to identify potential candidate items; formulation of new items compatible with the QLQ-C30 item style; expert evaluations and patient interviews; field-testing and psychometric analyses, including factor analysis, item response theory calibration and simulation of measurement properties. In addition, software for setting up, running and scoring CAT has been developed., Results: Across eight rounds of data collections, 9782 patients were recruited from 12 countries for the field-testing. The four phases of development resulted in a total of 260 unique items across the 14 domains. Each item bank consists of 7-34 items. Psychometric evaluations indicated higher measurement precision and increased statistical power of the CAT measures compared to the QLQ-C30 scales. Using CAT, sample size requirements may be reduced by approximately 20-35% on average without loss of power., Conclusions: The EORTC CAT Core represents a more precise, powerful and flexible measurement system than the QLQ-C30. It is currently being validated in a large independent, international sample of cancer patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: A recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival., Patients and Methods: A total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18)., Results: Both groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil-cisplatin arm only (p = 0.047). During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil-cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020)., Conclusion: Analyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil-cisplatin regimen as part of definitive CRT., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended., Methods: Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations., Findings: Of the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p=0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p=0.58). Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR)=0.39 [0.25-0.61]; p<0.0001), and again was not different from that in responding, randomised patients (p=0.40)., Interpretation: In patients with locally advanced thoracic oesophageal cancer, overall survival did not differ between responders to induction chemoradiation and patients having surgery after clinical failure of chemoradiation. Surgery should therefore be considered in those patients who are still operable., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer., Methods: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9)., Results: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items., Conclusion: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC., Patients and Methods: Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate., Results: A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively)., Conclusions: This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Circumferential resection margin (CRM) appears as a new powerful prognostic factor of survival after surgery for rectal cancer. We aimed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial. Patients with rectal cancer were randomised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin. Mesorectal excision was performed 6 weeks after treatment. Impact of clinical, pathological and surgical variables on positive CRM (≤1 mm) were analysed by multivariate analysis. Of 565 randomised patients, CRM was recorded in 390 cases and was positive in 8% (30/390). Patients with 50 Gy plus capecitabine and oxaliplatin had a 6% rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10% rate (p=0.128). Three independent predictive factors of positive CRM were identified: abdominoperineal resection (APR) (odds ratio OR=3.24; p=0.004), vascular tumour invasion (OR=2.78; p=0.026) and poor histological response (modified Dworak 0-2) (OR=9.01; p=0.003). Significant predictive factors of positive CRM are related to type of surgery, especially APR, and poor histological prognostic factors. Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC., Patients and Methods: Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 patients) and FFCD 9203 (756 patients) were pooled. Meta-analysis methodology was used to compare neoadjuvant CRT to RT for OS, PFS LC and distant progression (DP). Weighted linear regression was used to estimate trial-level association (surrogacy R(2)) between treatment effects on candidate surrogate (pCR, LC, DP) and OS., Results: The median follow-up was 5.6 years. Compared to RT (881 pts), CRT (886 pts) did not prolong OS, DP or PFS. The 5-y OS-rate was 66.3% with CRT versus 65.9% in RT (hazard ratios (HR) = 1.04 {0.88-1.21}). CRT significantly improved LC (HR = 0.54, 95%confidence interval (CI): 0.41-0.72). PFS was validated as surrogate for OS with R(2) = 0.88. Neoadjuvant treatment effects on LC (R(2) = 0.17) or DP (R(2) = 0.31) did not predict effects on OS., Conclusion: Preoperative CRT does not prolong OS or PFS. pCR or LC do not qualify as surrogate for PFS or OS while PFS is surrogate. Phase III trials should use OS or PFS as primary endpoint., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Health-related quality of life (HRQOL) questionnaires should ideally be adapted to the individual patient and at the same time scores should be directly comparable across patients. This is achievable using a computerised adaptive test (CAT). Basing the CAT on an existing instrument enables measurement within an established HRQOL framework and allows backward-compatibility with studies using the original instrument. Because of these advantages the EORTC Quality of Life Group (QLG) has initiated a project to develop a CAT version of the widely used EORTC QLQ-C30., Methods: We present the EORTC QLG's strategy for developing a CAT. For each dimension of the EORTC QLQ-C30 our approach includes literature search and conceptualisation, formulation of new items, expert and patient evaluations, field-testing, and psychometric analyses of the items. The strategy is illustrated with the initial results of the development of CAT for physical functioning (PF)., Results: We identified 975 PF items in the literature. Of these, 407 items were deemed relevant, i.e. measured one of the PF aspects measured by the QLQ-C30. Based on these items we developed 86 new items. Review by the EORTC CAT-project group reduced this to 66 items. Based on expert and patient evaluations several items were revised and the list was further reduced to 51 items., Conclusions: Based on the findings for PF, we believe that our approach will generate item pools that are relevant and appropriate for cancer patients. These will form the basis for a backward-compatible CAT assessing the HRQOL dimensions of the EORTC QLQ-C30., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

This international study aimed to test the measurement properties of the updated European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module for colorectal cancer, the QLQ-CR29. The QLQ-CR29 was administered with the QLQ-C30, core questionnaire, to 351 patients from seven countries. Questionnaire scaling and reliability were established and clinical and psychometric validity examined. Patient acceptability and understanding were assessed with a debriefing questionnaire. Multi-trait scaling analyses and face validity refined the module to four scales assessing urinary frequency, faecal seepage, stool consistency and body image and single items assessing other common problems following treatment for colorectal cancer. Scales distinguished between clinically distinct groups of patients and did not correlate with QLQ-C30 scales, demonstrating construct validity. The QLQ-CR29 scores were reproducible over time in stable health. The EORTC QLQ-CR29 demonstrates sufficient validity and reliability to support its use to supplement the EORTC QLQ-C30 to assess patient-reported outcomes during treatment for colorectal cancer in clinical trials and other settings.

Aim: To combine and test the EORTC questionnaires for assessing quality of life (HRQL) for oesophageal (QLQ-OES18) and stomach cancer (QLQ-STO22), into a single questionnaire for tumours of the oesophagus, oesophago-gastric junction or stomach., Methods: The QLQ-OES18, QLQ-STO22 and seven modified items were administered to 300 patients with oesophageal (n=148), junctional (n=66), or gastric cancer (n=86). Semi-structured interviews assessed item and scale preference and multi-trait scaling analyses confirmed the scale structure of the new module (QLQ-OG25). This was further tested for validity., Results: The QLQ-OG25 has six scales, dysphagia, eating restrictions, reflux, odynophagia, pain and anxiety. Scales have good reliability (alpha range 0.67-0.87) and they distinguish between tumour sites and disease stage. Scales do not correlate highly with scores from the core questionnaire, thus indicating that the module was addressing separate HRQL aspects., Conclusion: The QLQ-OG25 is recommended to supplement the EORTC QLQ-C30 when assessing HRQL in patients with oesophageal, junctional or gastric cancer.

The European Organisation for Research and Treatment of Cancer (EORTC) has a portfolio of questionnaire modules to supplement the QLQ-C30 to assess patient reported outcomes in cancer clinical trials. This study updated the module for colorectal cancer. A review of the literature identified 20 articles that used the EORTC colorectal module. Eight papers did not report data from scales addressing sexual function and 8 added additional scales to assess ano-rectal function. Interviews with patients (n=79) and professionals (n=11) informed item selection, reduction and modification. A new 29 item module was devised and further patient interviews (n=120) examined its format and content validity. Patients found the new module acceptable with relevant content. The new module, the EORTC QLQ-CR29, is hypothesised as containing 6 scales and 11 single items. An international study examining its clinical and psychometric validity will be performed.

The aim of this study was to identify factors associated significantly with hospitalised cancer patients' satisfaction with care. Patients were recruited from four geographical/cultural groups, including five European countries and Taiwan. They rated their level of satisfaction by completing the EORTC IN-PATSAT32 questionnaire at home. Additionally, data were collected on the sociodemographic and clinical characteristics and the quality of life of the patients, as well as on institutional characteristics. Of 762 patients recruited, 647 (85%) returned a completed questionnaire. The number of nurses and doctors per bed, institution size, geo-cultural origin, ward setting, teaching/non-teaching setting, treatment toxicity, global health status, participation in clinical trials and education level were all associated significantly at the multivariate level with satisfaction with doctor and nurse interpersonal skills, information provision, availability, and/or overall satisfaction. A number of patient-, institutional- and culture-related factors are associated with the perceived quality of cancer care. Future studies, with appropriate sampling frames and stratification procedures, are needed to better understand cross-national and cross-cultural differences in cancer patient satisfaction.

The purpose of this study was to determine whether baseline patients' self reported health-related quality of life (HRQOL) parameters could predict survival beyond key biomedical prognostic factors in patients with metastatic colorectal cancer. The analysis was conducted on 299 patients. HRQOL baseline scores were assessed using the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core30 (EORTC QLQ-C30). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. The final multivariate Cox regression model retained four variables as independent prognostic factors for survival: white blood cell (WBC) count with a hazard ratio (HR) of 1.961 (95% CI, 1.439-2.672; P<0.001), alkaline phosphatase with HR=1.509 (95% CI, 1.126-2.022; P=0.005), number of sites involved with HR=1.108 (95% CI, 1.024-1.198; P=0.01) and the patient's score on the social functioning scale with HR=0.991 (95% CI, 0.987-0.996; P<0.001) which translates into a 9% decrease in the patient's hazard of death for any 10 point increase. The independent prognostic importance of social functioning and the stability of the final Cox regression model were also confirmed by the additional bootstrap model averaging analysis, based on 1000 bootstrap-generated samples. The results suggest that social functioning, acts as a prognostic measure of survival beyond a number of previously known biomedical parameters.

The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

Little is known about patients' satisfaction with care in oncology hospitals across cultural contexts. Within the EORTC, we developed a 32-item satisfaction with care questionnaire to measure patients' appraisal of hospital doctors and nurses, as well as aspects of care organisation and services. This study assessed the psychometric characteristics of the questionnaire, the EORTC IN-PATSAT32, in a large, international sample of patients with cancer. Patients discharged from a surgery or medical oncology ward in nine countries were invited to complete at home the EORTC IN-PATSAT32 as well as other instruments for psychometric testing. Of 762 eligible patients recruited, 15% failed to return the questionnaire. Of the 647 compliant patients, 63% completed the questionnaires within 15 min and 82% required no help in its completion. Multitrait scaling analysis revealed excellent internal consistency and convergent validity, although some scales within the IN-PATSAT32 were relatively highly correlated. Test-retest data on 113 patients showed high reliability for most scales. Scales of the IN-PATSAT32 and of the QLQ-C30 were not significantly correlated, suggesting that the two questionnaires are assessing quite distinct concepts. The scales of the IN-PATSAT32 were able to discriminate clearly between patients with differing care expectations and differing intentions to recommend their hospital to others. This study supports the acceptability to patients, and the psychometric robustness of the EORTC IN-PATSAT32 questionnaire. Further studies are needed to assess the responsiveness of the questionnaire to changes in the structure and process of care over time.

The aim of this study was to assess the validity of the French version of the Functional Assessment of Cancer Therapy - General (FACT-G), and to compare its psychometric properties with those of two other cancer-specific quality of life questionnaires, European Organisation for Research and Treatment of Cancer Quality of Life - Core 30 (EORTC QLQ-C30) and Functional Living Index - Cancer (FLIC). Two hundred and twenty three patients with breast or colorectal cancer completed the FACT-G questionnaire in French followed by (in random order) the QLQ-C30 and FLIC. An additional 87 patients with head and neck (H&N) cancer completed the FACT-H&N followed by the QLQ-C30 and H&N-Besançon. The French version of FACT-G was internally consistent, and its reproducibility was excellent. FACT-G Physical Well-Being and global scores correlated with all QLQ-C30 subscales. There was evidence of discriminant validity. Compared with the other tools, FACT-G included a statistically significantly higher proportion of items patients considered to be confusing or upsetting. Patients with breast or colorectal cancer expressed a preference for QLQ-C30. Use of the specific H&N additional items increased the responsiveness to change of FACT-G. The French version of FACT-G is valid and has psychometric properties similar to those of FLIC and QLQ-C30.

The purpose of this study was to define the measurement properties and clinical validity of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module to assess health-related quality of life (HRQL) in gastric cancer. The EORTC gastric cancer module, QLQ-STO 22, was administered with the QLQ-C30, core questionnaire, to 219 patients undergoing treatment with curative or palliative intent before and after treatment. Reliability and validity of the module was tested and patients' debriefing comments analysed. Compliance rates were high, questionnaires well accepted and less than 4% of items had missing data. Multi-trait scaling analyses and face validity refined the module to five scales and four single items. Scales distinguished between clinically distinct groups of patients and demonstrated treatment-induced changes over time. Test-retest scores demonstrated good reliability. The EORTC QLQ-STO 22 demonstrates psychometric and clinical validity that supports its use to supplement the EORTC QLQ-C30 to assess quality of life in patients with gastric cancer undergoing surgery, surgery and chemoradiotherapy, palliative chemotherapy, palliative surgery and best supportive care.

Quality of life (QOL) assessment requires clinically relevant questionnaires that yield accurate data. This study defined measurement properties and the clinical validity of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module to assess QOL in oesophageal cancer. The oesophageal module the QLQ-OES24 and core questionnaire, the Quality of Life-Core 30 questionnaire (QLQ-C30) was administered patients undergoing treatment with curative (n=267) or palliative intent (n=224) and second assessments performed 3 months or 3 weeks later respectively. Psychometric tests examined scales and measurement properties of the module. Questionnaires were well accepted, compliance rates were high and less than 2% of items had missing data. Multi-trait scaling analyses and face validity refined the module to four scales and six single items (QLQ-OES18). Selective scales distinguished between clinically distinct groups of patients and demonstrated treatment-induced changes over time. The EORTC QLQ-OES18 demonstrates good psychometric and clinical validity. It is recommended for use with the core questionnaire, the QLQ-C30, to assess QOL in patients with oesophageal cancer.

Quality of life (QL) is an important outcome measure within clinical trials. This paper describes the development of a QL module for patients with liver metastases from colorectal cancer (CRC) to supplement the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, the EORTC QLQ-C30. Phases 1-3 of the EORTC QL Group guidelines for developing QL modules were followed. The literature search generated 71 QL issues. Semi-structured interviews with eight healthcare professionals and 47 patients from the United Kingdom, France, Germany and Austria reduced the list to 23 issues. Questionnaire items were formulated to be compatible with the EORTC QLQ-C30. The provisional module was further tested in 102 patients resulting in a 21-item module, the QLQ-LMC21 (Liver Metastases Colorectal). A combination of the core questionnaire and the QLQ-LMC21 will provide essential QL information regarding the use of treatments in both the curative and palliative settings.

Accurate assessment of health-related quality of life (HRQoL) in patients with advanced colorectal cancer is essential to improve our understanding of how cancer and chemotherapy influence patients' life and to adapt treatment strategies. Specific questionnaires have descriptive and predictive value and can be used to evaluate new therapies. Results from HRQoL assessments in randomised trials help patients and physicians to choose between treatment options. More than half of the patients treated with palliative chemotherapy have an improvement or at least a preservation of their HRQoL. However, several trials have found small differences in HRQoL between treatment groups. This may be due to the insufficient sensitivity of tools, low numbers of patients or missing data. An international consensus on the methods of measurement of HRQoL in oncology is warranted to enhance compliance, to better interpret results and to optimise the publication of precise HRQoL data.

Quality of life (QL) is an important outcome in clinical trials in oncology. There is currently no valid international QL measure for gastric cancer. This paper describes the development of a QL module for gastric cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ-C30) questionnaire. Phases I to III of module development were conducted in the United Kingdom, France, Germany and Spain according to EORTC QL Group guidelines. Twenty relevant QL issues were generated from the literature and interviews with health professionals (n=24) and patients (n=58). This produced a 24 item provisional module. Further testing in 115 patients resulted in the QLQ-STO22, containing 22 questions, conceptualised into five scales and four single items, related to disease symptoms, treatment side-effects and emotional issues specific to gastric cancer. The use of the QLQ-C30 supplemented by the QLQ-STO22 will provide a comprehensive QL measure for international trials in gastric cancer.

Patients with measurable or evaluable locally advanced or metastatic squamous cell carcinoma of the oesophagus were treated with cisplatin (CDDP), 100 mg/m2, combined with 5-fluorouracil (5-FU) at a dose of 1000 mg/m2 as a continuous infusion from days 1-5 (Arm A) or with CDDP alone (Arm B). Cycles were repeated every 3 weeks. 92 patients were randomised centrally, 88 were eligible. The response rate was 35% (95% CI (confidence interval), 20-54%) in Arm A and 19% (95% CI, 8-35%) in Arm B. One complete response was observed in each arm. The median duration of survival was 33 weeks and 28 weeks for Arm A and Arm B, respectively. Haematological and non-haematological toxicities were more frequent and more severe in Arm A. The most prominent toxicities were grade 4 aplasia and septicaemia (2), meningeal haemorrhage (1), cerebrovascular accident (3) and ischaemia of the lower limbs (1) all occurring in Arm A. Overall, seven treatment-related deaths (16%) were observed in Arm A, none in Arm B. The severe side-effects induced by the combination suggest that, currently, no standard chemotherapy can be recommended for patients with advanced squamous cell oesophageal cancer.

The objective of the present study was to define the role of chemotherapy, in the form of the EP regimen, consisting of epirubicin (E) and cisplatin (P) in addition to irradiation in combination with 5-fluorouracil (5-FU) for treatment of pancreatic cancer. 53 eligible patients with histologically or cytologically proven locally advanced pancreatic cancer were treated with three cycles of E 60 mg/m2 (if this dose was well tolerated then the dose of E was increased by 10 mg/m2 in the next cycle; 80 mg/m2 was the maximum dose for the following cycles) and P 100 mg/m2 once every 3 weeks, followed after 4 weeks by a split course of irradiation of 40 Gy with 5-FU 500 mg/m2 on each of the first 3 days of each 20 Gy treatment segment. This was followed by another three cycles of EP in patients who achieved stable disease (SD) or a better response after the first three cycles. The treatment given with standard anti-emetics was moderately tolerated. The chemotherapy related toxicity consisted mainly of myelosuppression and the chemoradiotherapy related toxicity of gastrointestinal side-effects. However, due to the long duration of treatment which made the whole treatment difficult to endure, only 18/53 (34%) actually completed the full treatment regimen. Responses were evaluated after the first three cycles and 4 weeks after the completion of the treatment by serial CT-scans using standard criteria. The results in 53 evaluable patients after the first three cycles of EP were as follows: 1 patient achieved a clinical complete response (CR), 7 a partial response (PR) (CR + PR: 15%; 95% confidence interval (CI): 11-33%), 36 patients (68%) had stable disease (SD) and 6 patients progressive disease (PD). There was 1 early PD, 1 toxic death and 1 patient could not be evaluated. The response at the end of the treatment was 3 CR, 11 PR (CR + PR: 14/53 (26%); 95% CI: 15-40%), 30 SD and 6 PD. The median time to progression was 8.9 months and the median duration of response 13.1 months. The median survival of all treated patients was 10.8 months (range 7 days to 41.5 months), of responders 15.1 months and, of the patients with SD 10.3 months. These results are comparable to other combined modality regimens reported in the literature for locally advanced disease. The addition of the systemic treatment with E and P offers no additional advantage to combined modality treatment alone.

This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.